The laboratory has actively investigated the molecular mechanisms of action of several human cytokines including, IL 2, IL 3, GM-CSF, and erythropoietin (Epo). IL 2 and other hematopoietic cytokines were shown to regulate tyrosine phosphorylation in situ. Although the receptors for these cytokines do not contain intrinsic kinase domains, the data suggested that they are in a tight association with one or more tyrosine kinases. We have developed specialized methods to isolate in vitro the tertiary structure of the IL 2 receptor subunits and the kinase responsible for the transmembrane signal. These methods are designed to facilitate the biochemical purification and subsequent molecular cloning of this associated receptor specific protein kinase. In addition, we have examined the cytoplasmic domains of the Epo receptor through mutation and functional analysis and have deduced the regions required for growth promotion and protein kinase coupling. The laboratory has molecularly cloned five new human protein kinases which are expressed in normal and leukemic tissues. One tyrosine kinase designated RLK appears to be a member of a unique family of PTK recently discovered in 1990. This kinase has two catalytic domains and contains some domain similarities to the c-fms proto-oncogene. We have assigned this gene to human chromosome 1 and have found that IFNGamma upregulates the mRNA of this gene in human monocytes. The laboratory has identified a transcriptional regulatory element found within the promoter regions of the IL 1RAlpha gene and the homologous element in the Human Immunodeficiency Virus-1 long terminal repeat. This protein was purified, and found to be under the control of a cytoplasmic inhibitor. The activation of this protein in situ was inhibited by cyclosporin A, suggesting that certain pharmacological inhibitors can block HIV transcription at this level.